Distribution of FMR1 and FMR2 repeats in 2 Argentinean patients with primary ovarian 3 insufficiency

Abstract

The premutation state of FMR1 has been associated with Fragile X-related Premature Ovarian 29 Failure (POI) and is the most common known genetic cause for 46,XX patients. Nevertheless, very 30 few studies analyzed its frequency in Latin American populations. Additionally, a relationship 31 between alleles carrying a cryptic microdeletion in the 5?UTR of FMR2 and the onset of POI has only 32 been studied in one population. 33<br />Our aim was to analyze the incidence of FMR1 premutations and putative microdeletions in 34 exon 1 of FMR2 in a cohort of Argentinean women with POI. We studied 133 patients and 84 35 controls. Fluorescent PCR was performed and the FMR2 exon 1 was further sequenced in samples 36 presenting less than 11 repeats. We found the frequency of FMR1 permutations to be 6.7% and 37 2.9% for familial and sporadic patients, respectively. Among controls , 1/84 women presented a 38 premutation. In addition, although we did not find microdeletions in FMR2 , we observed a change 39 (T>C) adjacent to the repeats in two sisters with POI. Given the repetitive nature of the sequence 40 involved, we could not ascertain whether this represents a SNP or a deletion. Therefore, a 41 relationship between FMR2 and POI could not be established for our population.